Pharmacology · Corticosteroids (glucocorticoids)
Hydrocortisone !
The pharmaceutical form of cortisol, the body's own stress hormone. It is the replacement of choice when the adrenal glands fail.
Updated 2026-11-01
Also called: Cortisol
The figure shows cortisol (hydrocortisone itself) in the ligand-binding domain of the human glucocorticoid receptor.
Mechanism of action
Hydrocortisone is identical to cortisol. It binds the glucocorticoid receptor, which enters the nucleus and changes gene transcription: anti-inflammatory and metabolic genes are switched on and pro-inflammatory ones repressed. Unlike synthetic analogues it also has some mineralocorticoid action, so at replacement doses it covers part of the salt-retaining need.
- Hydrocortisone (cortisol) binds the glucocorticoid receptor
- The drug-receptor complex moves into the nucleus
- It switches on anti-inflammatory genes and represses NF-κB and AP-1
- Fewer cytokines, prostaglandins and immune cells reach the tissue
Pharmacokinetics
- Absorption
- Well absorbed by mouth; the sodium succinate form is given IV or IM
- Metabolism
- Mostly in the liver; in the kidney part is turned into inactive cortisone
- Half-life
- Short-acting compared with synthetic glucocorticoids
Indications
- Primary or secondary adrenal insufficiency, including adrenal crisis (IV) Adrenal insufficiency →
- Congenital adrenal hyperplasia
- Severe allergic reactions, as an adjunct to adrenaline Anaphylaxis →
- Severe asthma and inflammatory bowel disease flares Ulcerative colitis →
Adverse effects
Common
- Fluid retention and higher blood pressure at higher doses
- Hyperglycaemia
- Insomnia and mood changes
- Acne
- Irregular menstrual periods
Contraindications
- Systemic fungal infections
- Hypersensitivity to the product
- Live or live attenuated vaccines during immunosuppressive doses
Key interactions
- CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, barbiturates)
- Faster clearance and a weaker corticosteroid effect
- Strong CYP3A4 inhibitors (ketoconazole)
- Higher corticosteroid levels and more side effects
- Aspirin and other NSAIDs
- Higher risk of gastrointestinal ulcer and bleeding
- Potassium-depleting drugs (loop or thiazide diuretics, amphotericin B)
- Hypokalaemia; with digoxin, more risk of arrhythmia
- Warfarin
- The anticoagulant response changes; INR is checked more often
What is monitored
- Blood glucose
- Blood pressure and weight
- Potassium
- Signs of infection
- Eye pressure and bone density with long use
Administration and safety
- For adrenal crisis the sodium succinate injection is given IV; it is reconstituted as the product label describes
- Replacement doses are split through the day to mimic the natural cortisol rhythm
- Patients on replacement need extra («stress») cover during illness or surgery, as ordered
Nursing care
- In adrenal crisis, check blood pressure, glucose, sodium and potassium closely
- Watch for infection: fever and other signs may be blunted
- Watch mood and sleep; report agitation, depression or confusion
- Teach that a long course is not stopped suddenly; it is tapered under medical supervision
- Teach people on replacement to carry an alert card and to seek care if vomiting stops them keeping tablets down
Pregnancy and breastfeeding
Used in pregnancy when the benefit justifies it; newborns of mothers on substantial doses are watched for adrenal insufficiency.
Test yourself
Think of the answer, then tap the question to see it.
Why is hydrocortisone the drug of choice for adrenal insufficiency?
It is cortisol itself, with glucocorticoid and some mineralocorticoid action; in primary disease it is often combined with fludrocortisone.
A patient with Addison disease has gastroenteritis and cannot keep tablets down. What is the risk?
Adrenal crisis: hypotension, shock, hyponatraemia, hyperkalaemia and hypoglycaemia. Parenteral hydrocortisone is needed urgently.
Which enzyme in the kidney inactivates cortisol to cortisone?
11β-hydroxysteroid dehydrogenase type 2, which protects the mineralocorticoid receptor from cortisol.
Related drugs
Related conditions
← Back to the class: Corticosteroids (glucocorticoids)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Hydrocortisone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); DailyMed - HYDROCORTISONE SODIUM SUCCINATE injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Farmacología básica y clínica (Katzung), 16.ª ed., cap. 39 (McGraw Hill, 2025).
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Representative model, for educational purposes only.